A collaborative approach to designing an online nutrition education program for people with multiple sclerosis.

PURPOSE: People with multiple sclerosis (pwMS) want disease-specific dietary advice to reduce the confusion around diet. This study used co-design principles to develop an online nutrition education program for pwMS. METHODS: Mixed-methods (multiphase sequential design). Phase 1: online survey (n = 114 pwMS) to explore preferred content and characteristics of a nutrition program and develop a draft program. Phase 2: feedback on the draft program from stakeholders (two meetings; n = 10 pwMS and multiple sclerosis (MS) health professionals) and pwMS (two workshops; n = 6) to produce a full program prototype. Phase 3: cognitive interviews (n = 8 pwMS plus 1 spouse) to explore acceptability and ease of comprehension of one module of the program, analysed using deductive content analysis. RESULTS: Preferred topics were included in the program, which were further developed with consumer feedback. Cognitive interviews produced four themes: (1) positive and targeted messaging to motivate behaviour change; (2) "not enough evidence" is not good enough; (3) expert advice builds in credibility; and (4) engaging and appropriate online design elements are crucial. CONCLUSIONS: Positive language appears to improve motivation to make healthy dietary changes and engagement with evidence-based nutrition resources. To ensure acceptability, health professionals can use co-design to engage consumers when developing resources for pwMS.IMPLICATIONS FOR REHABILITATIONCo-designed nutrition education programs can help people achieve high-quality diets in line with recommendations, but very few programs exist for people with multiple sclerosis (MS), and none were co-designedThe participatory research in this study was instrumental in ensuring that important information regarding program acceptability was identifiedCo-design can ensure that the language is appropriate for the target audience, and positive language appeared to improve motivation in people with MS to engage with the online nutrition education programWhere practical and feasible, health professionals should collaborate with MS consumers when developing resources, and use positive, empowering language.

mTOR Regulation of N-Myc Downstream Regulated 1 (NDRG1) Phosphorylation in Clear Cell Renal Cell Carcinoma.

The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected clear cell renal cell carcinoma (ccRCC) relative to pair-matched normal renal tissue. Using a proteomic array, we found N-Myc Downstream Regulated 1 (NDRG1) showed the greatest increase (3.3-fold) in phosphorylation (on Thr346) in ccRCC. This was associated with an increase in total NDRG1. RICTOR is a required subunit in mTORC2, and its knockdown decreased total and phospho-NDRG1 (Thr346) but not NDRG1 mRNA. The dual mTORC1/2 inhibitor, Torin 2, significantly reduced (by ~100%) phospho-NDRG1 (Thr346). Rapamycin is a selective mTORC1 inhibitor that had no effect on the levels of total NDRG1 or phospho-NDRG1 (Thr346). The reduction in phospho-NDRG1 (Thr346) due to the inhibition of mTORC2 corresponded with a decrease in the percentage of live cells, which was correlated with an increase in apoptosis. Rapamycin had no effect on ccRCC cell viability. Collectively, these data show that mTORC2 mediates the phosphorylation of NDRG1 (Thr346) in ccRCC. We hypothesize that RICTOR and mTORC2-mediated phosphorylation of NDRG1 (Thr346) promotes the viability of ccRCC cells.

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

Nutrition Education Programs for Adults with Neurological Diseases Are Lacking: A Scoping Review.

The nutrition recommendation for most common neurological diseases is to follow national dietary guidelines. This is to mitigate malnutrition, reduce the risk of diet-related diseases, and to help manage some common symptoms, including constipation. Nutrition education programs can support people in adhering to guidelines; hence the aim of this scoping review was to explore what programs have been implemented for adults with neurological diseases. We conducted this review according to a published a priori protocol. From 2555 articles screened, 13 were included (dementia n = 6; multiple sclerosis n = 4; stroke survivors n = 2; Parkinson's n = 1). There were no programs for epilepsy, Huntington's, and motor neurone disease. Program duration and number of sessions varied widely; however, weekly delivery was most common. Just over half were delivered by dietitians. Most did not report using a behavior change theory. Commonly used behavior change techniques were instruction on how to perform a behavior, credible source, and behavioral practice/rehearsal. Evidence of nutrition education programs for adults with neurological diseases is lacking. Of those that are published, many do not meet best practice principles for nutrition education regarding delivery, educator characteristics, and evaluation. More programs aligning with best practice principles are needed to assess characteristics that lead to behavior change.

The Adipose Tissue-Derived Secretome (ADS) in Obesity Uniquely Induces L-Type Amino Acid Transporter 1 (LAT1) and mTOR Signaling in Estrogen-Receptor-Positive Breast Cancer Cells.

Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of 3H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.

The RNA sensor MDA5 detects SARS-CoV-2 infection.

Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I and III IFN induction further required MAVS and IRF3. In contrast, induction of IL6 and TNF was independent of the MDA5-MAVS-IRF3 axis in this setting. We further found that SARS-CoV-2 infection inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 as a cellular sensor for SARS-CoV-2 infection that induced type I and III IFNs.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.

Dietary education programs for adults with neurological diseases: a scoping review protocol.

OBJECTIVE: The objective of this review is to identify and map the evidence on the types of dietary education programs that have been implemented and evaluated in any setting for adults with neurological diseases. This review will also examine program characteristics, including program duration, length, and number of sessions, and common behavior change techniques used. INTRODUCTION: Up to 1 billion people are affected by neurological diseases, most commonly Alzheimer's disease and dementias, epilepsy, Huntington's disease, motor neurone disease, multiple sclerosis, Parkinson's disease, and stroke. Dietary recommendations for most of these diseases follow national dietary guidelines. Dietary education programs are recommended by the World Health Organization to promote adherence to a healthy diet, but it is not clear which dietary education programs have been conducted for adults with neurological diseases or the characteristics of such programs. INCLUSION CRITERIA: This review will consider qualitative and intervention studies (randomized controlled trials, non-randomized controlled trials, and pre-post studies) evaluating dietary education programs for adults with neurological diseases. Programs can be any format in any setting, and may include a comparator group (waitlist control, treatment as usual, or another intervention) or have no comparator group. METHODS: CINAHL, Cochrane Database of Systematic Reviews, Emcare, MEDLINE, ProQuest (ProQuest Central and ProQuest Dissertations & Theses), PsycINFO, Cochrane Central Register of Controlled Trials, and Google Scholar will be searched for publications in English. Neurological organizations will be contacted for unpublished literature. Titles and abstracts will be screened, and full texts accessed for final inclusion. Intervention details, study outcomes, behavior change techniques, and findings will be extracted. Results will be presented in a table with accompanying description.

Expression of poly-ADP-ribose polymerase (PARP) in endometrial adenocarcinoma: Prognostic potential.

BACKGROUND: In the United States endometrial carcinoma is the most common female gynecologic malignancy. An average of more than 60,000 new cases of endometrial carcinomas have been diagnosed yearly over the past 5 years, with a higher incidence occurring in the central Appalachian states of Ohio and West Virginia. In the U.S., the national average of newly diagnosed endometrial carcinomas is 26.8 in every 100,000 women, while in the states of Ohio and West Virginia the average is 30.5 and 31.1 in every 100,000 women, respectively. This notable increase in the incidence of endometrial carcinomas may be due a variety of elevated risk factors including but not limited to: tobacco use, obesity, and genetic predisposition of the predominant demographic. The American Cancer Society estimates that approximately 55,000 new cases of endometrial carcinoma will be diagnosed in 2020 yet, this disease is widely considered understudied and under-represented in mainstream cancer research circles. METHODS: The aim of this study was to quantitate the co-expression of two DNA repair proteins poly-ADP-ribose polymerase 1 and 2 (Parp-1 and Parp-2) by enzyme- linked immuno-sorbent assay (ELISA) in 60 endometrioid endometrial tumor samples and compare their expression to matched non-malignant endometrial tissue from the same corresponding donors from central Appalachia. RESULTS: We found that Parp-1 was significantly overexpressed in endometrial carcinoma relative to corresponding normal tissue. This overexpression implicates Parp inhibition therapy as a possible treatment for the disease. Our results also found a protective effect of native Parp-2 expression in non-malignant endometrial tissue with each 1 ng/mL increase in PARP-2 concentration in normal tissue was associated with a 10 % reduction in the hazard of tumor progression (HR = 0.90; p = 0.039) and a 21 % reduction in the hazard of death (HR = 0.79; p = 0.044). CONCLUSIONS: This study demonstrated the over-expression of the druggable target Parp-1 in endometrial adenocarcinoma and observed a strong negative correlation of native Parp-2 expression and disease progression via the quantification of the Parp proteins using enzyme- linked immuno-sorbent assay (ELISA) assays.

A 3D Probabilistic Deep Learning System for Detection and Diagnosis of Lung Cancer Using Low-Dose CT Scans.

We introduce a new computer aided detection and diagnosis system for lung cancer screening with low-dose CT scans that produces meaningful probability assessments. Our system is based entirely on 3D convolutional neural networks and achieves state-of-the-art performance for both lung nodule detection and malignancy classification tasks on the publicly available LUNA16 and Kaggle Data Science Bowl challenges. While nodule detection systems are typically designed and optimized on their own, we find that it is important to consider the coupling between detection and diagnosis components. Exploiting this coupling allows us to develop an end-to-end system that has higher and more robust performance and eliminates the need for a nodule detection false positive reduction stage. Furthermore, we characterize model uncertainty in our deep learning systems, a first for lung CT analysis, and show that we can use this to provide well-calibrated classification probabilities for both nodule detection and patient malignancy diagnosis. These calibrated probabilities informed by model uncertainty can be used for subsequent risk-based decision making towards diagnostic interventions or disease treatments, as we demonstrate using a probability-based patient referral strategy to further improve our results.

Thrombospondin-1 Is a Major Activator of TGF-ß Signaling in Recessive Dystrophic Epidermolysis Bullosa Fibroblasts.

Mutations in the gene encoding collagen VII cause the devastating blistering disease recessive dystrophic epidermolysis bullosa (RDEB). RDEB is characterized by severe skin fragility and nonhealing wounds aggravated by scarring and fibrosis. We previously showed that TSP1 is increased in RDEB fibroblasts. Because transforming growth factor-ß (TGF-ß) signaling is also increased in RDEB, and TSP1 is known to activate TGF-ß, we investigated the role of TSP1 in TGF-ß signaling in RDEB patient cells. Knockdown of TSP1 reduced phosphorylation of smad3 (a downstream target of TGF-ß signaling) in RDEB primary fibroblasts, whereas overexpression of collagen VII reduced phosphorylation of smad3. Furthermore, inhibition of TSP1 binding to the LAP/TGF-ß complex decreased fibrosis in engineered extracellular matrix formed by RDEB fibroblasts, as evaluated by picrosirius red staining and analyses of birefringent collagen fibrillar deposits. We show that collagen VII binds TSP1, which could potentially limit TSP1-LAP association and subsequent TGF-ß activation. Our study suggests a previously unreported mechanism for increased TGF-ß signaling in the absence of collagen VII in RDEB patient skin. Moreover, these data identify TSP1 as a possible target for reducing fibrosis in the tumor-promoting dermal microenvironment of RDEB patients.

In the setting of paediatric osteomyelitis do not be afraid to CAST an eye.

The case commences with an innocuous right ankle injury (lateral malleolus), for which the patient, a 9-year-old boy, was placed in a temporary cast at his local hospital. Three days following this incident, the patient was diagnosed with new-onset type 1 diabetes mellitus. He was admitted to his local hospital with severe diabetic ketoacidosis appropriately treated and subsequently discharged c.1 week later clinically well. Approximately 1 week later, again he presented for a third time with a significant serosanguinous discharge from the site of the initial injury permeating through the temporary cast in place for c.2 weeks by that time. On removal of the cast, a severely invasive infection of bone and soft tissue was noted, and the patient was urgently transferred to our unit at the tertiary general hospital for further management. He underwent a series of orthopaedic and plastic surgery procedures with an eventual satisfactory outcome.

Performance of Pediatric Risk of Mortality Score Among Critically Ill Children With Heart Disease.

OBJECTIVE: To evaluate the performance of the Pediatric Risk of Mortality 3 (PRISM-3) score in critically ill children with heart disease. METHODS: Patients <18 years of age admitted with cardiac diagnoses (cardiac medical and cardiac surgical) to one of the participating pediatric intensive care units in the Virtual Pediatric Systems, LLC, database were included. Performance of PRISM-3 was evaluated with discrimination and calibration measures among both cardiac surgical and cardiac medical patients. RESULTS: The study population consisted of 87,993 patients, of which 49% were cardiac medical patients (n = 43,545) and 51% were cardiac surgical patients (n = 44,448). The ability of PRISM-3 to distinguish survivors from nonsurvivors was acceptable for the entire cohort (c-statistic 0.86). However, PRISM-3 did not perform as well when stratified by varied severity of illness categories. Pediatric Risk of Mortality 3 underpredicted mortality among patients with lower severity of illness categories (quintiles 1-4) whereas it overpredicted mortality among patients with greatest severity of illness category (fifth quintile). When stratified by Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STS-EACTS) categories, PRISM-3 overpredicted mortality among the STS-EACTS mortality categories 1, 2, and 3 and underpredicted mortality among the STS-EACTS mortality categories 4 and 5. Pediatric Risk of Mortality 3 overpredicted mortality among centers with high cardiac surgery volume whereas it underpredicted mortality among centers with low cardiac surgery volume. CONCLUSION: Data from this large multicenter study do not support the use of PRISM-3 in cardiac surgical or cardiac medical patients. In this study, the ability of PRISM-3 to distinguish survivors from nonsurvivors was fair at best, and the accuracy with which it predicted death was poor.

Astrocytes Resist HIV-1 Fusion but Engulf Infected Macrophage Material.

HIV-1 disseminates to diverse tissues and establishes long-lived viral reservoirs. These reservoirs include the CNS, in which macrophage-lineage cells, and as suggested by many studies, astrocytes, may be infected. Here, we have investigated astrocyte infection by HIV-1. We confirm that astrocytes trap and internalize HIV-1 particles for subsequent release but find no evidence that these particles infect the cell. Astrocyte infection was not observed by cell-free or cell-to-cell routes using diverse approaches, including luciferase and GFP reporter viruses, fixed and live-cell fusion assays, multispectral flow cytometry, and super-resolution imaging. By contrast, we observed intimate interactions between HIV-1-infected macrophages and astrocytes leading to signals that might be mistaken for astrocyte infection using less stringent approaches. These results have implications for HIV-1 infection of the CNS, viral reservoir formation, and antiretroviral therapy.

Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.

Relationship between risk-adjustment tools and the pediatric logistic organ dysfunction score.

BACKGROUND: The Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) method and Aristotle Basic Complexity (ABC) scores correlate with mortality. However, low mortality rates in congenital heart disease (CHD) make use of mortality as the primary outcome measure insufficient. Demonstrating correlation between risk-adjustment tools and the Pediatric Logistic Organ Dysfunction (PELOD) score might allow for risk-adjusted comparison of an outcome measure other than mortality. METHODS: Data were obtained from the Virtual PICU Systems database. Patients with postoperative CHD between 2009 and 2010 were included. Correlation between RACHS-1 category and PELOD score and between ABC level and PELOD score was examined using Spearman rank correlation. Consistency of PELOD scores across institutions for given levels of case complexity was examined using Kruskal-Wallis nonparametric analysis of variance. RESULTS: A total of 1,981 patient visits among 12 institutions met inclusion criteria. Positive correlations between PELOD score and RACHS-1 category (r s = .353, P < .0001) as well as between PELOD score and ABC level (r s = .328, P < .0001) were demonstrated. Variability in PELOD scores across individual centers for given levels of case complexity was observed (P < .04). CONCLUSIONS: Risk-Adjusted Classification for Congenital Heart Surgery categories and ABC levels correlate with postoperative organ dysfunction as measured by PELOD. However, the correlation was weak, potentially due to limitations of the PELOD score itself. Identification of a more accurate metric of morbidity for the congenital heart disease population is needed.

High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse.

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy. IMPORTANCE The ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spread in vivo and the specificities of neutralizing antibody elicited by antibody-based vaccines.

High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy.

OBJECTIVE: Few studies have examined the efficacy of antiretroviral therapy (ART) in the context of cell-to-cell transmission. We aimed to determine whether the activity of ART is limited by the mode of HIV-1 spread between cells and the type of immune cell implicated in transmission, or is independent of these variables. DESIGN: ART activity was evaluated in primary cells using in-vitro cell-free and cell to-cell HIV-1 infection systems. METHODS: HIV-1 cell-free or cell-to-cell transmission between infected monocyte-derived macrophages (MDMs) and autologous target CD4+ T cells was measured in the presence or absence of reverse transcriptase and integrase inhibitors. Viral infection was evaluated using luciferase-reporter infectious molecular HIV-1 clones carrying macrophage-tropic envelope glycoproteins (Envs). Cell-free HIV-1 was titrated to yield different multiplicities of CD4+ T-cell infection. RESULTS: Whereas cell-free infection of CD4+ T cells was substantially reduced by all inhibitors, cell-to-cell spread from macrophages to CD4+ T cells was largely resistant to inhibition. However, when multiplicity of infection was controlled for, we observed no difference in antiretroviral inhibition of cell-to-cell or cell-free infection. CONCLUSION: Cell-to-cell spread of HIV-1 reduces the probability of antiretroviral inhibition, but it is the number of infectious viruses transferred between cells rather than the specific mode of viral spread or transmitting cell type that governs antiretroviral activity. High multiplicity infection in vivo is more likely to occur by cell-to-cell transmission, and these data will inform use of ART against viral reservoirs.

Bilateral pulmonary artery banding as rescue intervention in high-risk neonates.

BACKGROUND: Presentation in shock and preoperative infection remain risk factors for neonatal cardiac surgery. This report describes bilateral pulmonary artery banding (bPAB) in ductal-dependent lesions with systemic outflow obstruction as rescue intervention before surgery with cardiopulmonary bypass in these high-risk neonates. METHODS: A retrospective chart review was conducted for 10 patients who underwent bPAB before conventional surgery with cardiopulmonary bypass. Patient characteristics including birth weight, gestational age, cardiac and noncardiac diagnoses, preoperative and postoperative markers of organ function, and outcome measures were examined. RESULTS: The majority of patients (8 of 10) were considered high-risk owing to multiorgan dysfunction syndrome. The median age at bPAB was 12 days (range, 5 to 26 days), and the median interval between bPAB and second surgery was 10.5 days (range, 5 to 79 days). Organ function improved after admission and continued to improve after bPAB in 9 of 10 patients. No patient experienced new complications between bPAB and subsequent operation. Of 8 patients who had stage I palliation, 5 have undergone or are awaiting completion Fontan, 1 underwent Kawashima procedure, 1 underwent orthotopic heart transplant, and 1 with hypoplastic left heart syndrome and intact atrial septum died at 44 days old. Both patients who underwent biventricular repair are alive and well. Median follow-up for survivors was 2.9 years (range, 0.25 to 6.25 years). CONCLUSIONS: Bilateral pulmonary artery banding is safe in ductal-dependent lesions with systemic outflow obstruction. High-risk patients with preoperative organ dysfunction or infection can recover within a short period and become lower risk candidates for complex congenital heart surgery using cardiopulmonary bypass.